Ovarian cancer is one of the most lethal gynecological malignancies, asymptomatic early progression, ineffective screening, and high histological heterogeneity. Accurate subtype classification and detection of chemotherapy resistance are critical for guiding personalized treatment strategies. Raman spectroscopy offers a label-free, non-destructive means of capturing biochemical fingerprints of cells, but its clinical potential is hindered by high spectral complexity and subtle inter-class variations. This study presents a machine learning-assisted Raman spectroscopy framework for the classification of ovarian cancer cell subtypes and their cisplatin resistance phenotypes. Raman spectra were acquired from normal ovarian epithelial cells (IOSE-80), four ovarian cancer cell lines (A2780, SKOV3, OVCAR-3, ES-2), and cisplatin-resistant variants (A2780-DDP, SKOV3-DDP). Three computational models were developed and systematically compared: a principal component analysis-support vector machine (PCA-SVM) algorithm and two convolutional neural network (CNN-Enhance and CNN-BiLSTM). Classification performance was assessed across three tasks: (i) discrimination of normal versus malignant cells, (ii) differentiation of cancer cells from their cisplatin-resistant variants, and (iii) classification of distinct cancer subtypes. Results show that Raman spectra reveal distinctive biochemical differences between normal and malignant cells, particularly in protein-, lipid-, and nucleic acid-related peaks. Both PCA-SVM and CNN achieved high classification accuracy (>90%) in most tasks, with PCA-SVM demonstrating greater stability and superior performance in subtype classification, while CNN showed advantages in specific cell-type detection. Notably, PCA-SVM achieved up to 100% accuracy in differentiating cisplatin-resistant phenotypes. These findings demonstrate that integrating Raman spectroscopy with machine learning enables label-free, and accurate classification of ovarian cancer subtypes and drug resistance, offering a promising pathway toward minimally invasive precision diagnostics and personalized cancer treatment planning.

Ferroptosis offers a promising potential for effective cancer therapy, promoting Fenton reaction-mediated lipid peroxidation to induce cell death; moreover, the implementation of ferroptosis can overcome the previous issue of drug resistance associated with conventional treatments. Covalent organic frameworks (COFs) are organic materials that exhibit crystallinity, porosity, surface functionality, drug delivery, and biocompatibility. This review discusses the unique functionalities of COFs, including framework, nanopore, surface area, and surface functionalizability, which effectively induce ferroptosis in cancer therapy while minimizing side effects on healthy tissues. To the best of our knowledge, this represents the first review to focus on the COFs for ferroptosis-based cancer therapy. This review also describes a synergistic combination of the COFs and ferroptosis-inductive molecular delivery. Furthermore, we highlight the potential of combinatorial ferroptosis cancer therapy, which can be effectively achieved by utilizing the multifunctionality of COFs, thereby synergizing with photodynamic therapy, photothermal therapy, chemodynamic therapy, sonodynamic therapy, radiotherapy, and immunotherapy. Ultimately, we discuss the challenges associated with scalability, biocompatibility, cancer-specific targetability, effective delivery, stimulus responsiveness, and multifunctionality of the COFs that need to be overcome to fully utilize unique advantages of the COFs in the clinics.

Although neoadjuvant chemotherapy (NACT) is commonly used for advanced ovarian cancer, patient outcomes vary substantially. We developed a graph convolutional network (GCN) that integrates patient-specific baseline clinical variables and computed tomography-derived radiomic features while modeling inter-patient relationships to improve outcome prediction beyond standard models. The GCN operates without reliance on high-performance computing resources and predicts long-term overall survival (OS) while stratifying short-term surgical outcomes (R0 resection). The GCN was compared with the CA-125 ELIMination rate constant K (KELIM) score and three Cox-based comparator models. Model performance was evaluated using the concordance index (C-index) for OS, area under the receiver operating characteristic curve for 3-year OS, Kaplan-Meier survival analysis, and R0 resection stratification. The GCN demonstrated strong OS prognosis performance (C-index = 0.73, 0.72, and 0.70 across the training and two external test datasets), stratified surgical outcomes, and identified 16.30% of patients with low KELIM scores but favorable survival.

A β-galactosidase-activatable photosensitizer, Scy-β, was rationally designed and synthesized, enabling near-infrared fluorescence/photoacoustic (NIFL/PA) dual-modal imaging of ovarian cancer, selective ovarian cancer cell killing, and efficient induction of immunogenic cell death (ICD). This study provides a novel tool for light-driven immunotheranostics of ovarian cancer.

Abstract Objective To evaluate the feasibility and accuracy of a sprayable γ-GGT fluorescent probe for visualizing epithelial ovarian cancer (EOC) across three hierarchical models (organoids, frozen sections, and ex vivo tissues), with a focus on optimizing its clinical applicability in intraoperative lesion detection. Methods This prospective study, leveraging a medical-engineering collaborative γ-GGT probe, was conducted in three phases: preliminary validation, ex vivo tissue optimization, and clinical validation. Initially, TCGA analysis and immunohistochemistry confirmed γ-GGT overexpression in epithelial ovarian cancer (EOC), with organoids and frozen sections employed to evaluate the probe’s specificity at both cellular and microstructural levels. Subsequently, fresh EOC tissues (n = 42 lesions from 8 patients) were treated with varying concentrations of the probe (1 μM, 5 μM, or 10 μM) to ascertain the minimal effective concentration (10 μM) and the optimal observation window (1 min–1 h) using signal-to-background ratio (SBR) analysis. Finally, clinical validation involved imaging 27 lesions (< 0.3 cm) and adjacent normal tissues from 8 patients, assessing the probe’s sensitivity (96.3% true positive rate) and false-positive rates (3.7%). Results Initial validation in ovarian cancer organoids and frozen sections demonstrated precise colocalization of γ-GGT probe fluorescence with immunohistochemical staining (DAB), confirming target specificity at cellular and microstructural levels. In ex vivo tissues (42 lesions from 16 patients), the 10 μM probe concentration achieved superior signal-to-background ratios (SBR = 1.40 ± 0.17 for primary lesions, 1.32 ± 0.12 for omental metastases) compared to 1 μM (1.17 ± 0.08) and 5 μM (1.27 ± 0.10) concentrations (P < 0.05). The probe consistently visualized lesions across all diameters (0.5 cm: SBR 1.40 ± 0.17; < 0.3 cm: SBR 1.41 ± 0.18; P > 0.05), with optimal imaging stability observed 1 min-1 h post-application (SBR range:1.26–1.29). Clinical validation in 27 sub-0.3 cm lesions demonstrated 96.3% sensitivity (26/27 true positives) and 81.5% macroscopic detection rate, with one false positive (3.7%) in normal peritoneal tissue. Immunohistochemistry confirmed γ-GGT membrane expression in 100% of cancerous lesions (42/42 experimental group, 26/27 validation group) versus absent expression in normal tissues. Univariate analysis identified preoperative serum γ-GGT levels (≥ 20 U/L: SBR 1.28 ± 0.13 vs < 20 U/L: 1.23 ± 0.18, P = 0.005) and treatment modality (P = 0.001) as significant factors, though only treatment approach remained independently predictive in multivariate analysis (P < 0.001). Conclusion The γ-GGT probe enables rapid, accurate EOC visualization at clinically relevant scales, with 10 μM concentration and 1 min–1 h window being optimal for intraoperative use. Hierarchical validation from cellular to tissue models underscores its translational potential.

In this work, an unconventional Se-substituted hemicyanine dye (HCySe-O-NO2) decorated with a p-nitrophenyl moiety as a recognition site was investigated. Its type I/II photosensitization processes could be regulated by the tumor microenvironment, alleviating the oxygen dependence of conventional photodynamic therapy (PDT) for the treatment of solid tumors. Upon being exposed to 760-nm-wavelength laser irradiation, cancer cells treated with HCySe-O-NO2 exhibited the phenomenon of pyroptosis, resulting in an amplification of cellular immunogenic death (ICD), and hence demonstrating the potential value of this dye for photoimmunotherapy.

The “Healthy China” initiative, along with advancements in technology for cancer diagnosis and treatment, has significantly enhanced outcomes for patients with gynecologic tumors. The trends of late marriage and delayed childbirth have led to an increasing number of women diagnosed with gynecologic cancers who are seeking fertility preservation in China. This issue is critical yet often overlooked in clinical practice. This review aims to synthesize the existing research on fertility preservation within the field of gynecologic oncology, emphasizing both clinical explorations and expert guidelines. We conducted a comprehensive literature review on fertility preservation in the context of gynecologic tumors, examining treatment approaches, commonly employed tumor management technologies, and specific techniques for preserving fertility. This extensive review highlights the importance of integrating fertility preservation strategies into treatment plans for gynecologic tumors. It explores various methods to safeguard fertility during chemotherapy, radiation therapy, and surgical interventions. For patients with early-stage cervical cancer, surgical options are available; however, these may result in obstetric complications. Neoadjuvant chemotherapy is currently under investigation as an alternative approach. Endometrial cancer can be managed through hysteroscopic resection combined with hormonal therapy. The feasibility of fertility preservation in ovarian cancer varies based on tumor type and patient age. In cases of vulvar and vaginal cancers, partial excision may be considered following a thorough evaluation. Chemotherapy for gestational trophoblastic tumors has proven effective and typically preserves fertility despite potential decreases in AMH levels. This review provides a comprehensive and current synthesis of the latest evidence and clinical practice guidelines regarding fertility preservation in gynecologic cancers. Its aim is to assist clinicians and researchers in addressing the urgent and increasing demand for effective fertility preservation strategies for their patients.

Background Ovarian cancer is a highly heterogeneous disease, with substantial variation in patients' responses to neoadjuvant chemotherapy (NACT ) and prognosis. Currently, specific stratification biomarkers for patient selection are lacking. Stratifying patients based on noninvasive imaging data prior to treatment could significantly improve treatment decisions. Methods Consensus clustering of pretreatment radiomic features from computed tomography images identified imaging subtypes in NACT patients. Five classifiers were developed for patient stratification in a subsequent cohort, and the biological behavior behind the radiomics-based clusters was explored. Results Consensus clustering identified four patient clusters, with consistent survival trends across both clustering and stable classifiers. Clusters 3 and 4 showed higher complete gross resection rates, longer overall survival, and more BRCA1 mutations, while clusters 1 and 2 had poorer prognoses and lower complete gross resection rates. Despite a higher tumor stage, cluster 4 was more sensitive to chemotherapies and targeted therapies. Cluster 2 had the lowest proportion of well-differentiated tumors, and upregulated genes were enriched in pathways related to epithelial mesenchymal transition and other classic cancer pathways. Weighted gene co-expression network analysis identified key modules and hub genes in clusters 1 and 2, with RNA signature scoring used for validation. Conclusions Stratification based on noninvasive imaging revealed distinct biological patterns among ovarian cancer patients, helping to identify subgroups with favorable responses to neoadjuvant chemotherapy and better survival outcomes, thereby facilitating more personalized treatment decisions.

Ovarian cancer progression is closely associated with tumor microenvironment (TME) dysregulation, particularly pathological angiogenesis driven by exosome-mediated crosstalk. Here, we elucidate that ovarian cancer-derived circPUM1 promotes angiogenesis by transferring to vascular endothelial cells via exosomes. Mechanistically, circPUM1 upregulates the expression of RAB27B and VEGFA by sponging miR-607, thus boosting release of exosome facilitated by RAB27B and directly activating VEGF signaling in endothelial cells to foster angiogenesis. To disrupt this circPUM1-driven TME modulation, we engineered an innovative pH-responsive 2D niobium carbide nanosheets loaded with circPUM1 siRNA. Through excessive PEI grafting, we functionalized the nanosheets with cationic property, achieving efficient negative-charged siRNA loading. Further surface PEGylation shielded the nanosheets' positive charge, reducing off-target effect and systemic toxicity, while acidic TME triggered PEG exfoliation for tumor-specific circPUM1 siRNA delivery. Functional cellular assays and an intraperitoneal tumor-bearing mouse model validated that the nanosheet-delivered circPUM1 siRNA effectively inhibited angiogenesis and peritoneal dissemination by knocking down circPUM1 expression and subsequently downregulating its downstream targets. This study uncovers a novel exosome-mediated angiogenesis mechanism and develops innovative MXene nanosheets for pH-responsive siRNA delivery providing a promising strategy for ovarian cancer precision therapy with significant clinical translational value and application potential.

Ovarian cancer (OC) peritoneal metastasis (OCPM) is a major cause of high mortality of OC, in which cancer cells incubated in ascites evolve various mechanisms to survive. Hippo/YAP singling plays multiple roles in carcinogenesis, however, its roles in OCPM have remained elusive. Here, we report that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Combined tandem mass tag- and tissue microarray-based proteomic studies revealed YWHAB down-regulation in post-neoadjuvant chemotherapy OCPM tissues, which was confirmed in no-neoadjuvant-chemotherapy-response tissues, isolated OCPM stem cells, and induced cisplatin-resistant cells. Knockdown of YWHAB promoted stemness and resistance in parental complete or near-complete primary OCPM and OVCAR3 cells in vitro and in vivo. Mechanistic study showed that YWHAB directly bound to YAP and promoted YAP cytoplasmic retention and thus YWHAB restriction promoted YAP activity and stemness in OCPM in the cells in which the Hippo/YAP signaling was constitutively activated by overloaded constitutively active YAP (YAP5SA), and the effect of YWHAB knockdown was significantly abolished. The SH3 binding domain in YAP is critical for YWHAB-YAP binding. Alteration in the 5mc methylation level in the YWHAB promoter was observed in OCPM stem cells. In summary, our results reveal that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Our findings suggest that YAP would be a therapeutic target for suppressing OCPM stemness caused by YWHAB restriction.

Objective: Primary Debulking Surgery (PDS) combined with platinum-based chemotherapy is the standard therapy for ovarian cancer. Some trials have suggested that neoadjuvant chemotherapy-Intermittent Debulking Surgery(NACT-IDS) can achieve equivalent efficacy in the chemotherapy of combining PDS, without influencing OS. This study aimed to explore the effects of NACT-IDS on the prognosis and platinum resistance of advanced ovarian cancer, so as to provide a certain basis for the selection of suitable clinical therapies. Methods: The patients with advanced ovarian cancer were selected from January 1, 2014 to January 1, 2017. The patients were assigned to NACT-IDS group or PDS group after evaluation by gynecological oncologists. We analysed the clinical data and collected the follow-up data of cases over 5 years. Results: Totally 173 patients were enrolled into the study, including 52 cases in NACT-IDS group and 121 cases in PDS group.The platinum-resistant relapse rate in NACT-IDS group was evidently greater than that in PDS group (22.9% vs 4.5%, P<0.001), and the multi-factor analysis results also proved that NACT (OR=7.822, 95%CI 2.121-28.855) was an independent risk factor for platinum-resistant relapse of ovarian cancer. No significant differences in PFS, RS and OS were found between two groups. Conclusion: NACT-IDS may increase the risk of platinum resistance, and it is not advisable to expand its indications blindly. During the IDS procedure, the surgical standard should aim for a more thorough tumor bed resection, achieving an R0 resection, in order to avoid the increased risk of recurrence. Precise selection of indications and comprehensive precision management throughout the treatment course are essential, as neoadjuvant chemotherapy does not necessarily affect prognosis.

Ovarian cancer (OC) is the most lethal gynecological malignancy worldwide, characterized by heterogeneity at the molecular, cellular and anatomical levels. Most patients are diagnosed at an advanced stage, characterized by widespread peritoneal metastasis. Despite optimal cytoreductive surgery and platinum-based chemotherapy, peritoneal spread and recurrence of OC are common, resulting in poor prognoses. The overall survival of patients with OC has not substantially improved over the past few decades, highlighting the urgent necessity of new treatment options. Unlike the classical lymphatic and hematogenous metastasis observed in other malignancies, OC primarily metastasizes through widespread peritoneal seeding. Tumor cells (the “seeds”) exhibit specific affinities for certain organ microenvironments (the “soil”), and metastatic foci can only form when there is compatibility between the “seeds” and “soil.” Recent studies have highlighted the tumor microenvironment (TME) as a critical factor influencing the interactions between the “seeds” and “soil,” with ascites and the local peritoneal microenvironment playing pivotal roles in the initiation and progression of OC. Prior to metastasis, the interplay among tumor cells, immunosuppressive cells, and stromal cells leads to the formation of an immunosuppressive pre-metastatic niche in specific sites. This includes characteristic alterations in tumor cells, recruitment and functional anomalies of immune cells, and dysregulation of stromal cell distribution and function. TME-mediated crosstalk between cancer and stromal cells drives tumor progression, therapy resistance, and metastasis. In this review, we summarize the current knowledge on the onset and metastatic progression of OC. We provide a comprehensive discussion of the characteristics and functions of TME related to OC metastasis, as well as its association with peritoneal spread. We also outline ongoing relevant clinical trials, aiming to offer new insights for identifying potential effective biomarkers and therapeutic targets in future clinical practice.

Although immune checkpoint inhibitors (ICIs) have transformed cancer treatment by improving survival, their ovarian safety remains uncertain. This study combined Mendelian randomization (MR) and experimental validation to assess the impact of PD-1 inhibitors on ovarian function. MR analysis used summary statistics from large European-ancestry genome-wide association studies (GWAS), applying the inverse-variance weighted (IVW) method, supported by sensitivity analyses. For in vitro experiments, mouse follicles were cultured with 10 µg/ml PD-1 inhibitor ch15mt (clinically relevant concentration), 200 nM doxorubicin (DOX), or PBS control. Follicular morphology was evaluated via diameter measurements; endocrine function by estradiol (E2) quantification using ELISA. Real-time cytoplasmic Ca²⁺ dynamics were monitored using FRET-based Cyto-Ca2 + probes for high-resolution stress assessment. MR results showed no significant association between genetically predicted PD-1 levels and risks of premature ovarian insufficiency, infertility, or alterations in ovarian hormones including AMH and E2. Sensitivity analyses confirmed MR robustness. In vitro, PD-1 inhibition did not affect follicular size or E2 secretion. Notably, DOX induced rapid Ca²⁺ elevation, while PD-1 inhibitor treatment had no detectable effect on Ca²⁺ fluctuations. This first integrative MR and experimental study demonstrates that PD-1 inhibitors at clinically relevant concentrations lack acute ovarian toxicity. While further work is needed to assess long-term effects, these findings demonstrate that standard anti-PD-1 immunotherapy regimens do not compromise follicular viability or endocrine function, strongly supporting their safety in fertility-sparing oncology protocols.

BackgroundLung cancer remains the leading cause of cancer-related deaths globally and represents the most common malignant tumor. While immunotherapy has significantly improved patient survival in recent years, the development of resistance limits its clinical efficacy. Currently, a systematic and comprehensive bibliometric analysis of drug resistance in immunotherapy for lung cancer is lacking. This study aims to address this gap by employing bibliometric methods to illuminate the knowledge structure and to identify key research hotspots in this critical area.MethodsWe retrieved publications concerning lung cancer immunotherapy drug resistance from the Web of Science Core Collection and PubMed databases, covering January 1, 2014, to December 31, 2024. NoteExpress was used for data integration, duplicate detection, and screening. Subsequently, we quantitatively and visually analyzed the characteristics of the selected literature, with an emphasis on country, institution, and keywords. This analysis was performed utilizing VOSviewer, CiteSpace, and the “bibliometrix” package in R.ResultThe annual publication output showed a marked upward trend, peaking in 2024. China produced the most publications, while the USA demonstrated higher citation impact. Analysis of keywords revealed a clear thematic evolution: from initial focus on clinical trials (e.g. Open-label) and specific drugs (e.g. Nivolumab), to immune checkpoints (e.g.PD-1/PD-L1), and more recently to underlying molecular mechanisms like the tumor microenvironment, autophagy, and ferroptosis.ConclusionsThis study offers a thorough overview of the most important research topics and emerging trends related to drug resistance and lung cancer immunotherapy. By integrating current knowledge, it enables researchers to swiftly identify pivotal research directions, thereby promoting in-depth development and innovation within the field and supporting the progression of clinical practice. For clinicians, this bibliometric insight provides a more scientific and precise basis for formulating treatment strategies, ultimately assisting lung cancer patients in deriving benefits from immunotherapy.

Improving the photosensitization efficiency represents a critical challenge in photodynamic therapy (PDT) research. While cyanines exhibit potential as photosensitizers (PSs) due to their large extinction coefficients and excellent biocompatibility, the inherent limitations in intersystem crossing severely affect therapeutic efficacy. Herein, we proposed a bottom-up magnetically enhanced photodynamic therapy (magneto-PDT) paradigm employing fluorobenzene-substituted pentamethine cyanine as type-I reactive oxygen species generators. Based on the radical pair mechanism and magnetic field effect, the notable difference in g-factors (Δg) between PSs and oxyradicals enabled magnetically responsive amplification of Cy5-3,4,5-3F-mediated hydroxyl radical (•OH) and superoxide anion radical (O2•-) production, achieving maximum yield enhancements of 66.9 and 28.0% respectively at 500 mT. This magnetically augmented oxyradicals generation exhibited universal cytotoxicity superiority over conventional PDT protocols in various cancer cell models. Notably, the semi-inhibitory concentration (IC50) of murine mammary carcinoma 4T1 cells demonstrated a remarkable reduction under both normoxic and hypoxic conditions, with the most pronounced decrease observed in normoxia from 0.91 μM (PDT alone) to 0.38 μM (magneto-PDT). The significantly magneto-enhanced therapeutic performance effectively inhibited orthotopic tumor growth. This magneto-PDT paradigm established a novel strategy for manipulating spin-dependent photosensitization processes in biological applications.

Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application. To address this limitation, a glutathione (GSH)‐responded nano‐herb delivery system (HA/MOS@OST&L‐Arg nanoparticles, HMOA NPs) is devised for the targeted delivery of OST with cascade‐activatable nitric oxide (NO) release. The HMOA NPs system is engineered utilizing enhanced permeability and retention (EPR) effects and active targeting mediated by hyaluronic acid (HA) binding to glycoprotein CD44. The cargoes, including OST and L‐Arginine (L‐Arg), are released rapidly due to the degradation of GSH‐responsive mesoporous organic silica (MOS). Then abundant reactive oxygen species (ROS) are produced from OST in the presence of high concentrations of NAD(P)H quinone oxidoreductase 1 (NQO1), resulting in the generation of NO and subsequently highly toxic peroxynitrite (ONOO−) by catalyzing guanidine groups of L‐Arg. These ROS, NO, and ONOO− molecules have a direct impact on mitochondrial function by reducing mitochondrial membrane potential and inhibiting adenosine triphosphate (ATP) production, thereby promoting increased apoptosis and inhibiting metastasis. Overall, the results indicated that HMOA NPs has great potential as a promising alternative for the clinical treatment of cervical cancer.

Tumor microenvironment is a rather unusual circumstances formed during the growth of tumor cells, showing significant differences from normal cells and tissues. Indeed, many biological active species (including enzymes, low pH, and small molecules) in the tumor microenvironment are used as triggered switches in the diagnosis and treatment of cancers. Compared with traditional cancer therapies, optical-based therapies such as photodynamic and photothermal therapies have opened up new avenues for clinical cancer treatment due to their excellent spatio-temporal selectivity, non-resistance, and non-invasiveness, among many other advantages. Intriguingly, in recent years, numerous organic phototheranostic agents based on tumor microenvironmental activation have been prepared, which can be specifically activated in tumor tissues and produce fluorescence to specifically visualize tumor tissues or activate the tumor cell death pathway by reactive oxygen species and heat generation to achieve tumor-specific ablation. In this review, we systematically describe the theranostic mechanism of agents, the design principles of activatable organic phototheranostic agents in response to the tumor microenvironment, their use for tumor-specific imaging and related applications in therapeutics. Additionally, the limitations of current activatable organic phototheranostic agents in clinical applications and the focus of future design directions are discussed.

127 Background: To explore the feasibility, accuracy and related influencing factors of spraying γ -GGT fluorescent probe in visual imaging of epithelial ovarian cancer. Methods: This study employed a previously developed spray-type γ-GGT fluorescent probe in fresh ex vivo epithelial ovarian cancer tissues. The experimental group selected ovarian cancer lesions of varying sizes and observed fluorescence imaging after spraying different concentrations of the probe. The optimal imaging concentration and observation time were determined based on pathological results. The validation group then used the optimal parameters to image primary and metastatic lesions, normal tissue, and suspicious areas, confirming the probe's accuracy. Clinical data from patients, such as age and stage, were analyzed to identify factors affecting probe imaging. Results: A total of 16 cases of epithelial ovarian cancer were included in this study, 8 cases were in the experimental group and 8 cases were in the validation group, and the samples were collected from the primary ovarian lesions, omental metastases and peritoneal metastases. In the experimental group, 42 lesions of 3 different diameters were collected. The visible lesions were not found to have any changes in the imaging within 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value within 1min-1h was between 1.26-1.29, with no statistical difference ( P>0.05), and the visible effect of 5 h was weaker or even invisible to the naked eye, and the best observation time was 1min-1h after spraying the γ-GGT fluorescent probe, and the SBR value of 1min-1h after spraying 10 μM of γ-GGT fluorescent probe was significantly higher than that of 1 μM and 5 μM ( P<0.05), and the best visible effect was achieved by the naked eye, resulting in a minimum effective imaging concentration of 10 μM. A total of 27 points were collected from the lesion with a diameter of <0.3 cm and its surrounding normal tissues with a distance of 1 cm or tissues with a diameter of 1-1.5 cm with a height of suspicion but normal to the naked eye, and 26 of the 27 tissues were confirmed by pathology to be cancerous and 1 was non-cancerous, with a true positive rate of 96.3% and a false positive rate of 3.7%. The overall true positive rate of fluorescence imaging was 98.6%. Univariate analysis showed that there were significant differences in the level of preoperative γ-GGT and the SBR value of preoperative treatment (all P<0.05), and the results of multivariate analysis showed that preoperative treatment was an independent influencing factor for fluorescence imaging of γ-GGT fluorescent probe ( P<0.05). Conclusions: This study tested the γ-GGT fluorescent probe for ovarian cancer imaging, finding 10 μM as the effective concentration and 1 minute to 1 hour as the optimal observation window. The probe's effectiveness is influenced by preoperative treatments.

122 Background: Ovarian cancer (OC) peritoneal metastasis (OCPM) is a significant cause of high mortality of OC. To investigate the mechanisms underlying OCPM stemness maintenance and resistance, we characterized proteomic alterations in residual OCPM tissues after neoadjuvant chemotherapy (NACT), and verified restriction of YWHAB-mediated YAP cytoplasmic retention as a novel important mechanism. Methods: Tumor specimens from HGSOC patients underwent proteomic analysis using TMT and REACTOME for pathway and GO analysis. The OVCAR3 cell line, derived from malignant ascites, and formalin-fixed samples were used for Immunohistochemistry. Ovarian cancer stem-like cells, including cisplatin-resistant cells, were cultured, and ALHD activity was measured by qPCR and ALDEFLUOR Kit. Western blot and Co-IP were used for protein analysis. Sphere formation and limiting dilution assays were performed in vitro and in vivo using BALB/c nude mice, and FACS quantified OCSCs. YWHAB-knockdown cells were created via plasmids, lentivirus, and transfection. Statistical tests included paired and unpaired t-tests, one-way ANOVA, and ELDA for limiting dilution. Data are shown as mean ± SD, with *p< 0.05, **p< 0.01, ***p< 0.001 indicating significance. Results: TMT-based proteomics identified 324 differentially expressed proteins in post-NACT OCPM tissues, with 179 upregulated and 145 downregulated. Bioinformatics revealed novel targets in key pathways, including TUBB, VCP in Hedgehog, YWHAB in Hippo, TLA1/2, SPTA1 in MAPK, and FASN in NOTCH. YWHAB downregulation was confirmed in pPR OCPM tissues and cells, serving as a marker to differentiate pNR from pCR/pPR OCPM (AUC = 0.7673). YWHAB inhibition in pCR OCPM cells enhanced stemness, as seen in sphere formation, OCSC percentages, CD133 expression, ALDH activity, and tumorigenicity. It also induced cisplatin resistance. YWHAB inhibition reduced cytoplasmic YAP retention and increased nuclear YAP, enhancing transcriptional activity. YAP5SA expression negated the effects of YWHAB depletion on stemness and resistance in pCR OCPM cells. Conclusions: In summary, this study explored the potential mechanisms underlying OCPM stemness maintenance and resistance by employing proteomic analysis, and revealed a novel YWHAB-mediated mechanism. This finding indicates that YAP would an important target for eradicating YWHAB-restricted OCSCs in OCPM.